The Impact of Concordance between Liquid and Tissue Biopsy for Actionable Mutations: Insights from the ROME Trial

PURPOSE: This analysis evaluated the influence of tissue and liquid biopsy concordance on outcomes in patients enrolled in the ROME trial. PATIENTS AND METHODS: The ROME trial, a phase II multicenter study, enrolled 1,794 patients with advanced solid tumors. Next-generation sequencing was performed on tissue and liquid biopsies using FoundationOne CDx and FoundationOne Liquid CDx. A centralized molecular tumor board reviewed results to identify actionable alterations, with 400 patients randomly assigned to tailored therapy (TT) or standard-of-care groups. TT improved objective response rate and progression-free survival (PFS) in the intention-to-treat population. Concordance was defined as the detection of the same druggable alteration in both biopsy types; discordance indicated detection in only one. RESULTS: Concordance was present in 49% of cases, with alterations detected exclusively in tissue (35%) or liquid (16%) biopsies. Patients in the concordant group receiving TT experienced improved survival outcomes. The median overall survival was 11.05 versus 7.70 months in the standard-of-care group [HR = 0.74; 95% confidence interval, 0.51-1.07], and the median PFS was 4.93 versus 2.80 months (HR = 0.55; 95% confidence interval, 0.40-0.76), respectively. In contrast, the survival benefit of TT was less pronounced or absent in patients with discordant results. Overall survival was higher in the T + L group (11.05 months), followed by tissue-only (9.93 months) and liquid-only (4.05 months) groups. PFS followed a similar pattern, with the longest PFS in the T + L group (4.93 months) versus 3.06 months in tissue-only and 2.07 months in liquid-only groups. CONCLUSIONS: The study highlights the potential value of integrating both biopsy modalities in selected clinical contexts. See related commentary by Saldanha and Siu, p. 7.